AKAP12alpha is Associated with Promoter Methylation in Lung Cancer / Journal of the Korean Cancer Association, 대한암학회지

ABSTRACT

PURPOSE: Promoter methylation is an important mechanism for silencing tumor-suppressor genes in cancer and it is a promising tool for the development of molecular biomarkers. The purpose of the present study was to investigate whether inactivation of the A Kinase Anchoring Protein 12 (AKAP12) gene is associated with promoter methylation in lung cancer. MATERIALS AND METHODS: The AKAP12 expression was examined by reverse transcription-polymerase chain reaction (RT-PCR) in ten lung cancer cell lines. The methylation status of the AKAP12alpha promoter was analyzed by performing bisulfite sequencing analysis in ten lung cancer cell lines, twenty four lung tissues and matched normal tissues. RESULTS: The AKAP12alpha expression was reduced in 6 of 10 (60%) lung cancer cell lines, whereas the AKAP12beta expression was absent in 1 of 10 (10%) lung cancer cell lines. The AKAP12alpha expression was restored after treatment with the demethylating agent 5-aza-2'-deoxycytidine in three lung cancer cell lines. Methylation of CpG island 1 in the AKAP12alpha promoter was detected in 30% of the lung cancer cell lines, whereas methylation of CpG island 2 in the AKAP12alpha promoter was observed in the immortalized bronchial cell line and in all the lung cancer cell lines. In lung tumors, the CpG island 1 in the AKAP12alpha promoter was infrequently methylated. However, CpG island 2 in the AKAP12alpha promoter was highly methylated in lung tumors compared with the surrounding normal tissues, and this was statistically significant (p=0.0001). CONCLUSION: Our results suggest that inactivation of the AKAP12alpha expression is associated with DNA methylation of the promoter region in lung cancer, and that AKAP12alpha may play an important role in lung cancer carcinogenesis.